Dose-dependent pancreatitis risk associated with GLP-1 agonists.

Objectives: Glucagon-like peptide 1 (GLP-1) receptor agonists have recently proven to be an effective treatment for type 2 diabetes mellitus (T2DM). However, these drugs are also known to carry a significant risk of drug-induced pancreatitis. The purpose of this study is to determine whether or not GLP-1-associated pancreatitis risk is dose-dependent. That is, we aim to determine whether the risk of developing pancreatitis increases with the administered dose of GLP-1 agonist or not. Methods: We conduct a retrospective case control study using data taken from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database. Participants are included if they reported an adverse effect of GLP-1 agonist and reported the cumulative dose of drug administered. We measure the odds ratio of developing pancreatitis between patients who have taken a large cumulative dose of GLP-1 agonist and those with a low cumulative dose of GLP-1 agonist. The odds ratio of different GLP-1 agonists are combined via a random effects model. Results: Patients with a high cumulative dose of GLP-1 agonist are associated with a higher risk of developing drug-induced pancreatitis associated with GLP-1 agonists, indicated by a statistically significant odds ratio. Furthermore, the odds ratio increases as the cumulative dose increases. Conclusions: GLP-1 agonists are associated with significant pancreatitis risk which increases with larger cumulative doses.